JP2012532681A - Antibacterial coating for invasive devices through the skin - Google Patents

Abstract

An antimicrobial coating applied to the percutaneous surface of a catheter device. The antimicrobial coating is applied to the percutaneous surface of the catheter device so that it is interposed between the catheter device and the patient's cortex when the catheter device is fully inserted.

Description

  The present invention relates to a coating for a dermally invasive device. In particular, the present invention relates to a method and system for applying an antimicrobial coating to the outer surface of a catheter device to prevent infection.

  Catheters are widely used for various infusion treatments. For example, catheters can be used to infuse fluids such as normal saline, various drugs and parenteral nutrition into the patient, withdraw blood from the patient, and monitor various parameters of the patient's vasculature Used.

  The catheter is typically introduced into the patient's vasculature as part of an intravenous catheter assembly. The catheter assembly generally includes a catheter hub that supports a catheter, and the catheter hub is coupled to a needle hub that supports an introducer needle. The introducer needle is extended and positioned within the catheter such that the needle ramp is exposed beyond the catheter tip. The inclined portion of the needle pierces the patient's skin to provide an opening so that the needle can be inserted into the patient's vasculature. After insertion and placement of the catheter, the introducer needle is removed from the catheter to provide intravenous access to the patient.

  Catheter-related bloodstream infections are caused by the formation of microbial colonies in the patient by intravascular catheters and IV access devices. These infections are an important cause of illness and increased medical costs, with approximately 250,000 catheter-related bloodstream infections occurring each year in the United States. In addition to monetary costs, these infections are associated with 20,000 to 100,000 deaths each year.

  Despite guidelines to help reduce healthcare associated infections (HAI), catheter-related bloodstream infections continue to plague medical systems. The 10 most common pathogens (accounting for 84% of HAI) are coagulase negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11 %), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Neisseria pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumania (3%) and Klebsiella oxytoka (2%). It was. The pooled mean proportion of pathogenic isolates resistant to antimicrobials varied widely across HAI types for several pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug resistant pathogens: Methicillin-resistant Staphylococcus aureus (8% of HAI), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant Pseudomonas aeruginosa (2%), substrate-specific extended-spectrum cephalosporin-resistant Klebsiella pneumoniae (1%), substrate-specific extended cephalosporin resistant E. coli (0.5%), and carbapenem resistant Acinetobacter baumania, Klebsiella pneumoniae, Klebsiella oxytoca and E. coli (0.5%) is there.

  Catheters impregnated with various antibacterial substances are one approach that has been implemented to prevent these infections. However, these catheters have not provided satisfactory results. In addition, several bacteria have developed resistance to various antimicrobial substances in the system.

  Therefore, there is a need in the art for an invasive device through the skin that has improved antimicrobial capabilities. Such methods and systems are disclosed herein.

  To overcome the above-mentioned drawbacks, the present invention provides an antimicrobial coating matrix applied to a catheter such that the antimicrobial coating is interposed between the catheter and the patient's cortex when the catheter device is fully inserted into the patient. is connected with.

  In some finished products, the antimicrobial formulation is provided as an insoluble coating material that is applied to the percutaneous region, surface or portion of the catheter device. The coating material is applied to prevent the coating from being exposed to the patient's vasculature. Thus, the patient's bloodstream is protected from exposure to the toxicity associated with antimicrobial prescriptions.

  In some implementations, the antimicrobial formulation is provided as a gel coat. Upon insertion of the catheter, the insertion site acts as a squeegee to remove excess gel coating from the catheter device. Since the excessive coating substance remains outside the insertion site, a pool of antibacterial substances is formed in the vicinity of the insertion site. In some embodiments, trace amounts of antimicrobial material remain integral to the percutaneous portion of the catheter device, and some of the antimicrobial material is transferred into the insertion site. In other embodiments, trace amounts of antimicrobial material remain integrally on the entire outer surface of the catheter so that some amount of antimicrobial material is exposed to the patient's bloodstream.

  In some embodiments, the antimicrobial formulation is provided as a moldable coating material. Upon insertion of the catheter, the insertion site acts as a wiping portion that removes excess moldable covering material from the catheter device. Since excess coating material remains outside the insertion site, a physical barrier is formed by manually molding the catheter and around the catheter insertion site. In some embodiments, the intravascular surface of the catheter is further modified as desired to include an anti-thrombogenic coating or lubricant as the likelihood of clotting increases.

  BRIEF DESCRIPTION OF THE DRAWINGS For the purposes of facilitating understanding of the above and other features and advantages of the invention, reference will now be made by way of example to a specific embodiment of the invention as illustrated in the accompanying drawings. A more detailed description of the invention described above is provided. The drawings illustrate exemplary embodiments of the invention and therefore should not be considered as limiting the scope of the invention.

1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antimicrobial coating. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antimicrobial coating. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antimicrobial coating and inserted into a patient. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antibacterial gel coating. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antibacterial gel coating upon insertion of a catheter into a patient. 1 is a side perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antimicrobial gel coating and inserted into a patient. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with a moldable antimicrobial coating. FIG. 1 is a side perspective view of a catheter device according to an exemplary embodiment of the present invention coated with a moldable antimicrobial coating and inserted into a patient. FIG. 1 is a side perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antibacterial gel coating and an antithrombotic lubricant. FIG. 1 is a side perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antimicrobial gel coating corresponding to the percutaneous and intravascular surface of the catheter device. FIG. 1 is a perspective view of a catheter device according to an exemplary embodiment of the present invention coated with an antibacterial gel coating upon insertion of a catheter into a patient. FIG. 4 is a top view of a catheter device and insertion site inserted with further protection with an antimicrobial dressing and skin prep treatment according to an exemplary embodiment of the present invention. 1 is a side perspective view of a catheter device coated with an antibacterial gel coating to be inserted into a patient, showing a catheter device including an antibacterial dressing and a skin pretreatment agent according to an exemplary embodiment of the present invention. FIG.

  The presently preferred embodiments of the present invention are best understood by referring to the drawings, wherein like reference numbers indicate identical or functionally similar elements. It will be readily appreciated that the components of the present invention can be arranged and designed for a wide variety of different configurations, as generally described and illustrated herein in the drawings. Accordingly, the following more detailed description as presented in the drawings is not intended to limit the scope of the claimed invention, but is representative of the presently preferred embodiments of the invention. It ’s just something.

  Referring to FIG. 1, a catheter device assembly system 10 is shown. In general, the catheter system 10 according to the present invention provides access to the vasculature 22 of a patient 20. In some embodiments, the catheter device system 10 includes a catheter hub 30 that supports a catheter tube 40. The catheter tube 40 extends outward from the catheter hub 30 and is in fluid communication with the catheter hub 30.

  In some embodiments, the catheter device system 10 further comprises a needle hub 50 that supports the introducer needle 60. The introducer needle 60 is positioned through the catheter hub 30 and the catheter hub 40 such that the inclined tip 62 of the needle 60 extends beyond the catheter tip 42. The angled tip 62 includes an incision surface that punctures the patient's skin 20 and provides access to the patient's vasculature 22. When the catheter 40 is fully inserted into the vasculature 22, the introducer needle 60 and needle hub 50 are removed, thereby providing intravenous access to the patient 20 via the catheter 40 and catheter adapter 30.

  The inserted catheter 40 is characterized as having a percutaneous region or surface 42 and an intravascular region or surface 44. The percutaneous surface 44 is referred to as the portion of the catheter 40 that traverses one or more cortical layers 24 of the patient 20 when the catheter 40 is fully inserted into the vasculature 22 of the patient 20. In some embodiments, the percutaneous surface 44 is referred to as the portion of the catheter 40 that is located within the patient 20 but not inserted into the vasculature 22. Further, in some embodiments, the percutaneous surface 44 is referred to as the portion of the catheter 40 that is not inserted into the vasculature 22 of the patient 20. Intravascular surface 46 is referred to as the portion of catheter 40 that is present in vasculature 22 after complete insertion of catheter 40. Thus, the length of each of the surfaces 44 and 46 may vary according to the type of catheter device system 10 and anticipated use.

  For example, if the catheter is used to access the patient's peripheral vasculature, the percutaneous surface 44 may be in the range of approximately 1 mm to approximately 6 mm. However, if the catheter is used to access a patient's non-peripheral vasculature, the percutaneous surface 44 may be in a length range from approximately 6 mm to approximately 700 mm. For example, such a catheter may include a central vascular catheter system.

  In some embodiments, an antimicrobial coating 70 is applied to the percutaneous surface 44 prior to insertion of the catheter 40. The covering 70 extends to the catheter 40 so that the covering 70 extends from the point of entry of the skin 20 to the inlet of the vein 22 after the catheter 40 is placed in the patient 20 and is near the cortex 24 of the skin 20. Applied. Thus, the coating 70 provides a protective barrier between the catheter 40 and the skin layer 24. The covering 70 further provides a protective barrier between the external environment 12 and the vasculature 22, thereby minimizing or avoiding the possibility of bacterial infection through the insertion site 14.

  In some embodiments, the coating 70 comprises a soluble or insoluble thin polymer matrix 72 disposed on the transdermal surface 44, as shown in FIG. As previously mentioned, the position of the matrix 72 is such that the percutaneous portion 44 extends from the point of the inlet 14 to the inlet of the vein 22 after the device 10 is deployed, as shown in FIG. The

  In some embodiments, the coating 70 comprises a viscous and lubricious gel matrix 74 disposed on the transdermal surface 44, as shown in FIG. 4A. Upon insertion of the catheter 40 into the patient 20, the insertion site 14 acts as a wiping portion that removes excess gel matrix 74 from the percutaneous surface 44. Since excess matrix 74 remains outside the patient, a reservoir 76 of matrix 74 is formed near the insertion site 14 and surrounds the insertion site 14.

  The reservoir 76 provides a physical barrier for the antimicrobial coating material 70, thereby further preventing unwanted microorganisms from being introduced into the insertion site 14. In some embodiments, a trace amount of matrix 74 remains integral with the transdermal surface 44 through the skin layer 24. Thus, the matrix 74 provides both external and internal protection for the insertion site 14. In some embodiments, the wiping function of the insertion site 14 removes the matrix 74 to provide a gradient of the coating 70 across the percutaneous surface 44. In other embodiments, the combination of the wiping function of the insertion site 14 and the solubility of the matrix 74 provides a gradient of the coating 70 across the transdermal surface 44.

  In some embodiments, the coating 70 comprises a conformable putty-like matrix 78 disposed on the transdermal surface 44 as shown in FIG. Upon insertion of the catheter 40 into the patient 20, the insertion site 14 acts as a wiping portion that removes excess matrix 78 from the percutaneous surface 44. Excess matrix 78 remains as a moldable mass 80 on the outside of the patient, as shown in FIG. And it is possible to cover the insertion site 14 and the area in the vicinity thereof by manually molding the moldable mass 80 as desired. In some embodiments, a trace amount of matrix 78 remains integral with the transdermal surface 44 through the skin layer 24. Thus, the matrix 78 provides both external and internal protection for the insertion site 14.

  Referring to FIG. 8, in some embodiments, the coating 70 includes a biocompatible dye material 90 that provides a continuous antimicrobial color indication. For example, in some embodiments, the dye material 90 exhibits a first color in the absence of microbial activity and a second color in the presence of microbial activity. Generally, the dye material 90 is positioned on the catheter 40 to be in the vicinity of the insertion portion 14. Thus, microbial activity in the vicinity of the insertion site 14 is indicated by the dye 90.

  In some embodiments, the catheter 40 further includes an antithrombotic lubricant 92 corresponding to the intravascular surface 46. The antithrombotic lubricant 92 reduces the likelihood of condensation on the intravascular surface 46 of the catheter 40. Accordingly, in some embodiments, the antithrombotic lubricant 92 is at least partially dissolvable to assist in the effectiveness and mobility of the antithrombotic properties. By limiting the placement of the coating 70 and the lubricant 92 to the target tissue, i.e., the portion of the catheter that will contact the cortex 24 and the vasculature 22, respectively, the coating 70 is limited while limiting the likelihood of condensation. The toxicity received from is minimized.

  Referring to FIG. 9, in some embodiments, the coating 70 is disposed over both the percutaneous surface 44 and the endovascular surface 46 of the catheter 110. When the catheter 110 is inserted, as described above and as shown in FIG. 10, the insertion site 14 acts as a wiping portion that removes the excess coating 70. In some embodiments, the remaining coating 70 remains integral with the percutaneous surface 44 and the endovascular surface 46 of the catheter 110, thereby providing antimicrobial protection over the entire length of the catheter 110. In some embodiments, the coating 70 is at least partially dissolvable to assist in the mobility and effectiveness of the coating. For example, if the coating 70 is at least partially soluble, the coating 70 will flow easily when it comes into contact with the body fluid of the patient 20. In some embodiments, the coating 70 is disposed over the entire length of the catheter 110 with a slope that increases or decreases from the catheter hub 30 to the catheter tip 42. Further, in some embodiments, the coating 70 includes a mixture of antimicrobial materials, antithrombotic lubricants, and biocompatible dye materials.

  In some embodiments, as shown in FIGS. 11 and 12, the catheter 40 and insertion site 14 are further combined with an antimicrobial insertion site preparation 100 and an antimicrobial dressing 102. For example, in some embodiments, the prospective insertion site 14 of the patient 20 is first pretreated with an antimicrobial modifier 100, such as an iodine scrub. Then, the catheter 40 and the introduction needle 60 are inserted into the insertion site 14. In some embodiments, as described above, the coating 70 forms a reservoir 76 that surrounds the insertion site 14. After insertion, the needle 60 is removed and the antimicrobial dressing 102 is provided as an external barrier to the catheter 40 and catheter adapter 30. Thus, in some embodiments, additional antimicrobial protection is provided to further protect the insertion site 14 from microbial activity.

  In general, the present invention relates to a novel antimicrobial prescription comprising an antimicrobial substance used to sterilize a catheter and a patient's catheter insertion site. As mentioned earlier, antimicrobial formulations can be provided in a variety of consistency and forms, allowing a variety of coating methods as desired. The coating of the antimicrobial substance (s) on the surface of the medical device prevents unwanted microbial growth and reduces microbial colonization on the medical device during normal use. That is, it prevents contamination of bacteria caused by contact with the bacterial flora of the patient's skin or by exposure to microorganisms prior to contact with the patient. In addition, reducing the colonization of microorganisms allows the medical device to remain in the patient for a longer time without causing infection.

  In some embodiments, it is provided as comprising a mixture of antimicrobial substances selected to provide a long-lasting antimicrobial effect even after multiple applications. For example, in some embodiments, the antimicrobial substance is selected and formulated from a polymer matrix that has very low water solubility. Thus, the antibacterial prescription will withstand multiple treatments such as blood collection, drug infusion, TPN treatment, as well as saline flush and heparin flush.

  In some tube embodiments, the antimicrobial coating 70 includes a matrix of one or more antimicrobial substances. A non-limiting example of the coating 70 is shown in Table 1.

For example, in some embodiments, coating 70 includes an alcohol component. Suitable alcohol components generally include lower alcohols having between 1 and 6 carbons (C ₁ -C ₆ ). In some embodiments, the coating 70 includes an alcohol component selected from the group consisting of ethyl alcohol, isopropanol, propanol, and butanol. Other embodiments include two or more lower alcohol components, such as a mixture of isopropyl alcohol and ethyl alcohol in a ratio of about 1:10 to about 1: 1. Further, in some embodiments, the coating 70 includes three or more alcohol components.

  In some embodiments, the coating 70 includes an alcohol component in an amount approximately equal to 40% (weight / volume) thereof. In other embodiments, the coating 70 includes approximately 20% (weight / volume) to approximately 95% (weight / volume) of the alcohol component.

  In some embodiments, the coating 70 further includes one or more fugitive solvents such as tetrahydrofuran (THF), methyl ethyl ketone (MEK) and hexanes solutions. In some embodiments, coating 70 includes an amount of labile solvent approximately equal to 40% (weight / volume) thereof. In other embodiments, the coating 70 includes two or more labile solvents.

  The antibacterial coating 70 generally includes antibacterial or bactericidal substances that are effective against various bacterial types and strains that can cause infection in the patient 20. The term “bactericidal substance” or “biocide” refers here to substances that destroy, inhibit and / or prevent the propagation, growth, colonization and multiplication of undesirable organisms. Referenced to. The term “organism” refers to microorganisms, bacteria, undulating bacteria, spirochetes, spores, spore-forming organisms, gram-negative organisms, gram-positive organisms, yeasts, filamentous fungi, fungi , Viruses, aerobic organisms, anaerobic organisms, and mycobacteria, but are not limited to these. Specific examples of such organisms include black Aspergillus, yellow Aspergillus flavus, black Rhizopus nigricans, Cladosprorium herbarium, Epidermophyton floccosum, Trichophyton fungus, Histoplasma capsulatum and other fungi; Pseudomonas aeruginosa, Escherichia coli, Proteus bulgaris, Staphylococcus aureus, Staphylococcus epidermis, Staphylococcus aureus, Klebsiella, Enterobacter aerogenes, Mirabilis variant Bacteria, other gram negative bacteria, and other gram positive bacteria, mycobactin and other bacteria; including Saccharomyces cerevisiae, Candida albicans and other yeasts. In addition, microbial spores and others are organisms within the scope of the present invention.

  Biocides suitable for use in the present invention include, but are not limited to, guanidine, phenol and quaternary ammonium containing biocides. For example, in some embodiments, the coating 70 comprises a biocide selected from taurolidine, parachlorometaxylenol, silver sulfadiazine, silver oxide, and silver nitrate. In other embodiments, the coating 70 comprises a biocide selected from a pyridinium biocide, benzaconium chloride, cetrimide, benethonium chloride, cetylpyridinium chloride, decalinium acetate, decalinium chloride, and chloroxylenol.

  Further, in some embodiments, the coating 70 comprises chlorhexidine base, chlorhexidine gluconate, chlorhexidine acetate, chlorhexidine hydrochloride, chlorhexidine dihydrochloride, dibromopropamidine, halogenated diphenylalkanes, carbanilide. Biocides selected from, salicylanilide, tetrachlorosalicylanilide, trichlorocarbanilide and mixtures thereof. Still further, in some embodiments, the coating 70 comprises chlorhexidine dihydrochloride, chlorhexidine gluconate, chlorhexidine acetate, chlorhexidine diacetate, triclosan, chloroxylenol, decalinium chloride, benzethonium chloride, and benzalkonium chloride thereof. Contains a biocide selected from the combination.

  In some embodiments, the coating 70 includes one or more biocides in an amount from about 0.01% (weight / volume) to about 10.0% (weight / volume) of the coating 70. In other embodiments, the coating 70 includes one or more biocides in an amount from about 0.01% (weight / volume) to about 5.0% (weight / volume) of the coating 70.

  In some embodiments, adding a cationic polymer to the formulation extended the life of the antimicrobial coating. By combining the cationic polymer with the antibacterial substance, an adhesion state to the surface of the medical device was formed. Thus, when the antibacterial substance was applied to the medical device, the coating solvent evaporated, leaving the antibacterial substance and the cationic polymer adhered to the medical device. Non-limiting examples of cationic polymers include cellulosic polymers, chitosan, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, polyurethane and water soluble cellulose. In some embodiments, the cationic polymer was selected as being soluble in alcohol but insoluble in water. In other embodiments, the cationic polymer was selected as being soluble in water.

  In some embodiments, the coating 70 is prepared by simply mixing the various components at room temperature. Typically, the organic solvent or alcohol and water are first mixed, followed by the addition of other components in any order. Formulations 1-11 in Table 1 were prepared with ingredients as shown in Table 2.

  The present invention may be embodied in other specific forms without departing from its structure, method, or other essential characteristics, as broadly described herein and as set forth in the appended claims. To get. For example, the present invention is applicable to any percutaneous invasive device, such as a needle, scalpel, trocar, endoscope, fistula instrument and the like. The described embodiments are to be considered in all respects as illustrative and not as restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes that come within the scope and meaning equivalent to the invention described in the claims are embraced within their scope.

Claims (21)

A catheter having a distal end, a proximal end and an extension therebetween, the catheter further having an outer surface including a percutaneous surface and an intravascular surface;
An antimicrobial substance applied to the percutaneous surface of the outer surface to intervene between the percutaneous surface and the patient's skin after insertion of the catheter into the patient;
An antibacterial catheter device characterized by comprising:   The device of claim 1, wherein the antimicrobial material comprises at least one of a water soluble coating, an insoluble coating, a viscous gel coating, a moldable matrix, and a solid coating. A polymer component;
An unstable solvent component; and
An alcohol component,
A biocidal substance,
An antibacterial composition comprising:   4. The composition of claim 3, wherein the biocide is a non-alcoholic biocide.   The composition according to claim 3, wherein the polymer component is a cationic polymer component.   The composition according to claim 3, wherein the polymer component is water-insoluble.   The composition according to claim 3, wherein the polymer component is water-soluble.   4. The composition of claim 3, wherein the amount of biocide present is from about 0.01% (weight / volume) to about 10.0% (weight / volume).   4. The composition of claim 3, wherein the amount of biocide present is from about 0.01% (weight / volume) to about 5.0% (weight / volume).   4. The composition of claim 3, wherein the amount of the polymer component present is from about 0.001% (weight / volume) to about 5.0% (weight / volume).   The composition according to claim 6, wherein the polymer component is at least one of a cellulosic polymer, chitosan, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, and polyurethane.   The biocide is at least one of chlorhexidine dihydrochloride, chlorhexidine gluconate, chlorhexidine acetate, chlorhexidine diacetate, triclosan, chloroxylenol, decalinium chloride, benzethonium chloride, and benzalkonium chloride. Item 4. The composition according to Item 3.   4. The composition of claim 3, wherein the alcohol component comprises a lower alcohol having between 1 and 6 carbon atoms.   The composition according to claim 3, wherein the amount of the alcohol component present in the antibacterial substance is approximately equal to 20% (weight / volume).   4. The alcohol component is a mixture of isopropyl alcohol and ethanol, and the amount present in the antibacterial substance is about 40% (weight / volume) to about 95% (weight / volume). A composition according to 1.   4. The composition of claim 3, wherein the labile solvent comprises an organic solvent present in the antimicrobial material in an amount of about 20% (weight / volume) to about 95% (weight / volume). .   The composition of claim 3, wherein the polymer component comprises a cationic polymer. A method for manufacturing an antimicrobial catheter device, comprising:
Providing a catheter having an outer surface;
Determining the percutaneous surface of the outer surface;
Determining the intravascular surface of the outer surface, and coating the transdermal surface with an antimicrobial substance;
A method characterized by that.   The method according to claim 18, further comprising the step of coating the intravascular surface with an antithrombotic substance.   The method of claim 18, wherein the antimicrobial material comprises a biocompatible bacterial indicator dye.   19. The method of claim 18, further comprising coating the inner blood vessel surface with an insoluble antimicrobial substance.

Images